Abstract

Introduction

CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit
prothrombotic and proinflammatory properties on binding to their cell surface receptor
CD40. The results of small clinical studies suggest that sCD40L levels could play
a role in sepsis; however, there are no data on the association between sCD40L levels
and mortality of septic patients. Thus, the aim of this study was to determine whether
circulating sCD40L levels could be a marker of adverse outcome in a large cohort of
patients with severe sepsis.

Methods

This was a multicenter, observational and prospective study carried out in six Spanish
intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10,
and plasma levels of tissue factor were measured in 186 patients with severe sepsis
at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched
controls. Survival at 30 days was used as the endpoint.

Results

Circulating sCD40L levels were significantly higher in septic patients than in controls
(P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity.
Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated
with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37
to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality
at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03).

Conclusions

In conclusion, circulating sCD40L levels are increased in septic patients and are
independently associated with mortality in these patients; thus, its modulation could
represent an attractive therapeutic target.